DACTINOMYCIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C62H86N12O16
Molecular Weight	1255.417
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@@]12CCCN1C(=O)[C@H](NC(=O)[C@@H](NC(=O)C3=C4N=C5C(OC4=C(C)C=C3)=C(C)C(=O)C(N)=C5C(=O)N[C@H]6[C@@H](C)OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@]7([H])CCCN7C(=O)[C@H](NC6=O)C(C)C)[C@@H](C)OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C2=O)C(C)C

InChI

InChIKey=RJURFGZVJUQBHK-IIXSONLDSA-N

InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C62H86N12O16
Molecular Weight	1255.417
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	10 / 10
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Dactinomycin (actinomycin D) was isolated from Streptomyces by Selman Waksman in 1940s. The antibiotic shows anti-cancer activity; it was approved by FDA for the treatment of different cancer conditions among which are Ewing's sarcoma, Wilm's tumor, gestational trophoblastic disease, etc. Dactinomycin exerts its action by binding to DNA (preferably to GC motif) and thus inhibiting transcription.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278	Binding Agent 1,064		156.25 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Wilms' tumor 1	Primary	Approved 8,429	COSMEGEN
Childhood rhabdomyosarcoma 1	Primary	Approved 8,429	COSMEGEN
Metastatic nonseminomatous testicular cancer 1	Primary	Approved 8,429	COSMEGEN
Ewing’s sarcoma 8	Primary	Approved 8,429	COSMEGEN
Gestational trophoblastic neoplasia 1	Primary	Approved 8,429	COSMEGEN
Locally recurrent and locoregional sarcomas 1	Palliative	Approved 8,429	COSMEGEN
Locally recurrent and locoregional carcinomas 1	Palliative	Approved 8,429	COSMEGEN
Locally recurrent and locoregional adenocarcinomas 1	Palliative	Approved 8,429	COSMEGEN

C_max

Value	Dose	Co-administered	Analyte	Population
30.3 μg/mL	3 mg/kg single, intravenous		DACTINOMYCIN plasma	Homo sapiens
35.5 ng/mL	1.5 mg/m² 1 times / day steady-state, intravenous		DACTINOMYCIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
142.4 mg × h/L	3 mg/kg single, intravenous	DACTINOMYCIN plasma	Homo sapiens
3.62 mg × min/L	1.5 mg/m² 1 times / day steady-state, intravenous	DACTINOMYCIN plasma	Homo sapiens
12.8 mg × min/L	1.5 mg/m² 1 times / day multiple, intravenous	DACTINOMYCIN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.8 h	3 mg/kg single, intravenous		DACTINOMYCIN plasma	Homo sapiens
28.5 h	1.5 mg/m² 1 times / day steady-state, intravenous		DACTINOMYCIN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
10%	3 mg/kg single, intravenous		DACTINOMYCIN plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
0.15 mg/kg 1 times / day multiple, intravenous Overdose	unhealthy, 18 months	Other AEs: Pancytopenia, Mucositis...
0.15 ug/kg multiple, intravenous Highest studied dose	unhealthy, 40-77 years
1.5 mg/m2 single, intravenous Highest studied dose	unknown, children

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AEs

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AE	Significance	Dose	Population
Hypocalcemia	1 patient	0.15 mg/kg 1 times / day multiple, intravenous Overdose	unhealthy, 18 months
Hyponatremia	1 patient	0.15 mg/kg 1 times / day multiple, intravenous Overdose	unhealthy, 18 months
Melena	1 patient	0.15 mg/kg 1 times / day multiple, intravenous Overdose	unhealthy, 18 months
Pancreatitis	1 patient	0.15 mg/kg 1 times / day multiple, intravenous Overdose	unhealthy, 18 months
Pancytopenia	1 patient	0.15 mg/kg 1 times / day multiple, intravenous Overdose	unhealthy, 18 months

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
abcr GmbH	AB353527	http://www.abcr.de/shop/en/AB353527
Achemtek	0104-058162	http://www.achemtek.com/50-76-0
Acorn PharmaTech	ACN-036884	http://www.acornpharmatech.com/
Ambinter	Amb19930304	http://www.ambinter.com/reference/19930304
Aurora Fine Chemicals LLC	A17.878.164	http://online.aurorafinechemicals.com/info?ID=A17.878.164

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PubMed

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Title	Date	PubMed
Inhibition of VCAM-1 expression in human bronchial epithelial cells by glucocorticoids.	1999 Apr	10100995
Venoocclusive liver disease (VOD) as a complication of Wilms' tumour management in the series of consecutive 206 patients.	2000 Oct	11194540
Polyphyenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells.	2001 Feb	11236827
Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells.	2001 Feb	11234897
Identification of manganese superoxide dismutase as a NO-regulated gene in rat glomerular mesangial cells by 2D gel electrophoresis.	2003 Dec	14996425

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Patents

Sample Use Guides

In Vivo Use Guide

Wilms’ Tumor, Childhood Rhabdomyosarcoma and Ewing’s Sarcoma: Regimens of 15 mcg/kg intravenously daily for five days administered in various combinations and schedules with other chemotherapeutic agents; Metastatic Nonseminomatous Testicular Cancer: 1000 mcg/m2 intravenously on Day 1 as part of a combination regimen with cyclophosphamide, bleomycin, vinblastine, and cisplatin; Gestational Trophoblastic Neoplasia: 12 mcg/kg intravenously daily for five days as a single agent. 500 mcg intravenously on Days 1 and 2 as part of a combination regimen with etoposide, methotrexate, folinic acid, vincristine, cyclophosphamide and cisplatin; Regional Perfusion in Locally Recurrent and Locoregional Solid Malignancies: 50 mcg (0.05 mg) per kilogram of body weight for lower extremity or pelvis, 35 mcg (0.035 mg) per kilogram of body weight for upper extremity.

Route of Administration: Intravenous

In Vitro Use Guide

Human osteosarcoma cell line MG63 were incubated with dactinomycin (actinomycin D) at final concentrations of 0.1, 0.5, 1 and 5 uM during 0, 2, 6 and 24 hours. The drug was shown to inhibit the proliferation of cells by decreasing cyclin gene transcriptions.

Substance Class	Chemical
Record UNII	1CC1JFE158
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DACTINOMYCIN

Official Name

English

DACTINOMYCIN [HSDB]

Common Name

English

ACTINOMYCIN C1

Common Name

English

ACTINOMYCIN D [WHO-IP]

Common Name

English

DACTINOMYCIN [WHO-IP]

Common Name

English

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Classification Tree

Code System

Code

DNA Minor Groove Binding Agent

NCI_THESAURUS

C204

Antineoplastic, immunosuppressives and medicines used in Palliative care

WHO-ESSENTIAL MEDICINES LIST

8.2

Enzyme Inhibitors

NDF-RT

N0000000233

Solid tumors

LIVERTOX

NBK548778

IARC

IARC

Actinomycin D

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Code System

Code

Type

Description

RS_ITEM_NUM

1162400

PRIMARY

HSDB

3220

PRIMARY

PUBCHEM

457193

PRIMARY

DRUG BANK

DB00970

PRIMARY

MERCK INDEX

m4067

PRIMARY

Merck Index

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Related Record

Type

Details


					22ES734693

MULTIDRUG RESISTANCE PROTEIN 1

TRANSPORTER -> SUBSTRATE


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

5 % (average)

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Related Record

Type

Details


					1CC1JFE158

DACTINOMYCIN

ACTIVE MOIETY

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Name	Property Type	Amount
Biological Half-life	PHARMACOKINETIC	36 hours (average)

Volume of Distribution	PHARMACOKINETIC	[0.84 to 10.2] Liters/Kilogram (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound